1,721,006 research outputs found
Characterization of KlGUT2, a gene of the glycerol-3-phosphate shuttle, in Kluyveromyces lactis
No full textMetabolic role of cGMP in S. cerevisiae: the murine phosphodiesterase-5 activity affects yeast cell proliferation by altering the cAMP/cGMP equilibrium
No full textIn higher eukaryotes, cAMP and cGMP are signal molecules of major transduction pathways while phosphodiesterases (PDE) are a superfamily of cAMP/cGMP hydrolysing enzymes, modulatory components of these routes. Saccharomyces cerevisiae harbours two genes for PDE: Pde2 is a high affinity cAMP-hydrolysing enzyme, while Pde1 can hydrolyse both cAMP and cGMP. To gain insight into the metabolic role of cGMP in the physiology of yeast, the murine Pde5a1 gene encoding a specific cGMP-hydrolysing enzyme, was expressed in S. cerevisiae pdeΔ strains. pde1Δ and pde2Δ PDE5A1-transformed strain displayed opposite growth-curve profiles; while PDE5A1 recovered the growth delay of pde1Δ, PDE5A1 reversed the growth profile of pde2Δ to that of the untransformed pde1Δ. Growth test analysis and the use of Adh2 and Adh1 as respiro-fermentative glycolytic flux markers confirmed that PDE5A1 altered the metabolism by acting on Pde1-Pde2/cyclic nucleotides content and also on the TORC1 nutrient-sensing cascade. cGMP is required during the log-phase of cell proliferation to adjust/modulate cAMP levels inside well-defined ranges. A model is presented proposing the role of cGMP in the cAMP/PKA pathway. The expression of the PDE5A1 cassette in other mutant strains might constitute the starting tool to define cGMP metabolic role in yeast nutrient signaling
Three target genes for the transcriptional activator Cat8p of Kluyveromyces lactis: acetyl coenzyme A synthetase genes KlACS1 and KlACS2 and lactate permease gene KlJEN1
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Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis.
No full textBACKGROUND & AIMS: Hyperfibrinolysis may complicate the clinical course of liver cirrhosis. The aim of this study was to evaluate if, in cirrhosis, hyperfibrinolysis is primary or secondary to intravascular clotting activation and if endotoxemia is associated with activation of clotting and/or the fibrinolytic system.
METHODS: Clotting, fibrinolytic indexes, and endotoxemia were studied in 41 cirrhotic patients and 20 healthy subjects.
RESULTS: Twenty-seven cirrhotic patients (66%) had high plasma levels of prothrombin fragment F1 + 2, a marker of thrombin generation. Nineteen patients had elevated values of D-dimer, a marker of fibrinolysis in vivo. All patients
with high values of D-dimer also had high values of prothrombin fragment F1 + 2. Endotoxemia was elevated in patients with severe liver failure and significantly
correlated to prothrombin fragment F1 + 2. Thirty patients were treated for 7 days either with standard therapy (n = 15) or with standard therapy plus nonabsorbable antibiotics (n = 15). Although standard therapy did not significantly change laboratory indexes, a significant reduction of endotoxemia, prothrombin fragment F1 + 2, and D-dimer was found in those patients who received the combined treatment.
CONCLUSIONS: This study shows that, in cirrhotic patients, hyperfibrinolysis is not a primary phenomenon but occurs as a consequence of clotting activation and that endotoxemia might play a pathophysiological role
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Kinetic properties of native and mutagenized isoforms of mitochondrial alcohol dehydrogenase III purified from Kluyveromices lactis
No full textBy computer modelling and protein engineering we have investigated changes in two amino acid residues located in the coenzyme pocket
of the yeast Kluyveromyces lactis mitochondrial alcohol dehydrogenase III. These two residues, Gly 225 and Ala 274, were hypothesized to
be involved in the enzyme discrimination between NAD(H) and NADP(H). Upon changing Gly 225 to Ala we produced an enzyme (mutant
G225A) showing very little difference from the wild-type. On the contrary, change at position 274 of Phe instead ofAla (mutantA274F) caused
a significant increase of Km values for NAD(P) and for NADPH and even a more marked decrease in catalytic activity. The kcat/Km rates for
NADP(H) were also decreased in this mutant. Enzymes with the double changes at 225 and 274 (mutant G225A-A274F) showed, apart the
substantial low Km value for NADPH and its high catalytic efficiency, kinetic parameters relative to coenzymes which were not additive over
the single substitutions. Surprisingly, enzymes with changes at the two positions reduced efficiently acetaldehyde, displaying a Km value
10-fold lower and a catalytic efficiency sevenfold higher with respect to parent or singularly mutated enzymes. None of the engineered
enzymes would convert formaldehyde, glutaraldehyde or aromatic aldehydes but all enzymes reduced propionaldehyde and butyraldehyde at
relative reaction rates approximately half of that exhibited by acetaldehyde. Interestingly only mutant A274F was able to oxidize methanol
almost as well as ethanol. In addition, this mutant was capable to convert secondary and cyclic alcohols, at a rate not detected in the other
isoforms. These results are in general agreement with the prediction that increasing the size of amino acids in the proximity of the coenzyme
pocket would hamper the accommodation of NADP but discord the increased affinity for NADPH as well as for alcoholic or aldehydic
substrates with high steric hindrance
Phosphodiesterase inhibitors: Could they be beneficial for the treatment of COVID-19?
Full text linkIn March 2020, the World Health Organization declared the severe acute respiratory syndrome corona virus 2 (SARS-CoV2) infection to be a pandemic disease. SARS-CoV2 was first identified in China and, despite the restrictive measures adopted, the epidemic has spread globally, becoming a pandemic in a very short time. Though there is growing knowledge of the SARS-CoV2 infection and its clinical manifestations, an effective cure to limit its acute symptoms and its severe complications has not yet been found. Given the worldwide health and economic emergency issues accompanying this pandemic, there is an absolute urgency to identify effective treatments and reduce the post infection outcomes. In this context, phosphodiesterases (PDEs), evolutionarily conserved cyclic nucleotide (cAMP/cGMP) hydrolyzing enzymes, could emerge as new potential targets. Given their extended distribution and modulating role in nearly all organs and cellular environments, a large number of drugs (PDE inhibitors) have been developed to control the specific functions of each PDE family. These PDE inhibitors have already been used in the treatment of pathologies that show clinical signs and symptoms completely or partially overlapping with post-COVID-19 conditions (e.g., thrombosis, inflammation, fibrosis), while new PDE-selective or pan-selective inhibitors are currently under study. This review discusses the state of the art of the different pathologies currently treated with phosphodiesterase inhibitors, highlighting the numerous similarities with the disorders linked to SARS-CoV2 infection, to support the hypothesis that PDE inhibitors, alone or in combination with other drugs, could be beneficial for the treatment of COVID-19
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